Ciita, short for MHC class II transactivator, is a master regulator of MHC class II (MHC-II) gene transcription. As a member of the NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein family, it plays a critical role in the activation and regulation of adaptive immunity through antigen presentation to CD4+ T cells [1,2,3]. The strict regulation of MHC-II expression by Ciita is crucial for proper immune responses. Genetic models, such as KO/CKO mouse models, are valuable for studying Ciita's functions.

FBXO11, an E3 ligase, regulates Ciita protein level through ubiquitination-mediated degradation, thereby affecting MHC-II expression at promoter, transcriptional, and surface levels [1]. Human and mouse FBXO11-deficient cells display increased levels of MHC-II and related genes, indicating the negative regulatory role of FBXO11 on Ciita-mediated MHC-II expression. In cancer, the expression of FBXO11, along with Ciita, is associated with prognosis [1].

In a rat model of Parkinson's disease, reduced Ciita levels significantly increase α-Syn pathology, nigrostriatal neurodegeneration and behavioral deficits, suggesting that Ciita regulates susceptibility to PD-like pathology through changes in resident and peripheral immune cells and TNF levels [4]. Also, in a Chinese family, a novel missense variant in the CIITA gene was identified in sisters with ovarian endometriosis, and the mutation affected cell migration and invasion ability, demonstrating that CIITA variants may contribute to the development of endometriosis [5].

In conclusion, Ciita is essential for regulating MHC-II gene expression and thus adaptive immunity. Studies using gene knockout models have revealed its significance in diseases like cancer, Parkinson's disease, and endometriosis. These findings contribute to understanding the underlying mechanisms of these diseases and may offer potential therapeutic targets.